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NAFLD and NASH

Fuelled by increasing obesity rates, NAFLD has emerged as a leading global cause of chronic liver disease in the past few decades. Despite growing prevalence, the factors influencing NAFLD development and subsequent progression to NASH, liver fibrosis, cirrhosis and hepatocellular carcinoma are poorly understood. In this article series, Nature Reviews Gastroenterology & Hepatology explores the epidemiology of NAFLD, disease mechanisms and therapeutics, and clinical aspects including screening, diagnosis and management.

Reviews and Perspectives

The prevalence of nonalcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC) is projected to continue to increase worldwide. In this Review, Huang, El-Serag and Loomba discuss the global epidemiology and risk factors for NAFLD-related HCC, and propose strategies to tackle this problem.

Review Article | | Nature Reviews Gastroenterology & Hepatology

This Review describes the pathophysiological roles of peroxisome proliferator-activated receptors (PPARs) in nonalcoholic steatohepatitis and related metabolic diseases, and summarizes the preclinical and clinical data on the use of PPAR agonists to treat nonalcoholic steatohepatitis as part of a systemic metabolic disease.

Review Article | | Nature Reviews Gastroenterology & Hepatology

Emerging data have revealed that nonalcoholic steatohepatitis (NASH) and fibrosis are associated with the reactivation of developmental pathways in the liver injury response. This Review describes the role of these pathways in liver development and in the pathogenesis of NASH and fibrosis.

Review Article | | Nature Reviews Gastroenterology & Hepatology

The gut microbiota has been linked to non-alcoholic fatty liver disease (NAFLD), but metabolic confounding factors, such as obesity and diabetes, complicate analysis. This Review provides a broad insight into microbiome signatures for human NAFLD and explores issues with disentangling them from underlying metabolic disorders.

Review Article | | Nature Reviews Gastroenterology & Hepatology

The hepatic consequence of metabolic syndrome and obesity, nonalcoholic fatty liver disease (NAFLD), underlies many cases of hepatocellular carcinoma (HCC). In this Review, the authors discuss NAFLD-associated HCC, including its epidemiology, key features that promote hepatocarcinogenesis and the management of HCC in patients with obesity.

Review Article | | Nature Reviews Gastroenterology & Hepatology

The liver is a key metabolic organ, and alterations to hepatic metabolism are important for the development of disease. In this Review, the authors explore the central roles of peroxisome proliferator-activated receptor-γ coactivators (PGC1s) in physiological and pathophysiological settings, with a focus on nonalcoholic fatty liver disease and liver cancer.

Review Article | | Nature Reviews Gastroenterology & Hepatology

The pathophysiology of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis is not yet completely understood but innate immunity is a major factor. In this Review, the evidence for macrophage involvement in the development of liver steatosis, inflammation and fibrosis is discussed.

Review Article | | Nature Reviews Gastroenterology & Hepatology

The combination of increasing disease prevalence and the prospect of approved pharmacological treatments has made the development of noninvasive biomarkers for NAFLD and NASH a research priority. In this Review, the authors comprehensively summarize the features of current and potential biochemical, imaging and genetic biomarkers.

Review Article | | Nature Reviews Gastroenterology & Hepatology

Nonalcoholic steatohepatitis is the progressive form of nonalcoholic fatty liver disease, one of the most common chronic liver diseases. In this Review, the authors comprehensively discuss the key factors that trigger hepatic inflammation, as well as the pathways involved in inflammation resolution.

Review Article | | Nature Reviews Gastroenterology & Hepatology

Cardiovascular disease is the leading cause of death in NAFLD. In this Review, the authors explore the evidence that NAFLD affects not only the coronary arteries but also all other cardiac structures, thereby potentially increasing risk of cardiomyopathy, cardiac arrhythmias, conduction defects and valvular calcification.

Review Article | | Nature Reviews Gastroenterology & Hepatology

The association between NAFLD and diabetes mellitus has garnered increasing attention in the past few years. In this Review, Tilg and colleagues explore in detail the molecular mechanisms linking NAFLD and diabetes mellitus, and discuss clinical aspects arising from the interaction of both diseases.

Review Article | | Nature Reviews Gastroenterology & Hepatology

Related news and commentaries

In 2020, there have been substantial advances in nonalcoholic fatty liver disease mechanisms, diagnostics and treatment. Key developments include the identification of a cellular and tissue signature to provide new insights into pathophysiology, advancements in non-invasive diagnostics and publication of interim results of the first phase III trial to demonstrate improvement in hepatic fibrosis.

Year in Review | | Nature Reviews Gastroenterology & Hepatology

On ‘International NASH Day’, we launch a call for the global health community to collaboratively shape and deliver a comprehensive, long-term public health agenda for NAFLD. A global multidisciplinary coalition is needed to guide our response to this increasingly prevalent, yet underaddressed disease.

Comment | | Nature Reviews Gastroenterology & Hepatology

Two new position papers convincingly propose that nonalcoholic fatty liver disease needs a new name — metabolic associated fatty liver disease (MAFLD). A new name for this disease affecting nearly one billion people globally is overdue, as knowledge gained from the past decades has assuringly demonstrated that MAFLD is a purely metabolic disorder.

News & Views | | Nature Reviews Gastroenterology & Hepatology

Advances have been made in the field of nonalcoholic fatty liver disease in 2019. One paper highlights the role of gut microbiota in hepatocellular carcinoma (HCC) pathogenesis, another presents a noninvasive algorithm for detecting advanced liver fibrosis and another suggests a potential novel approach to treating nonalcoholic steatohepatitis and suppressing HCC development.

Year in Review | | Nature Reviews Gastroenterology & Hepatology

The diagnostic reach of nonalcoholic fatty liver disease (NAFLD) is broad, stretching from simple steatosis to cirrhosis. Expanded disease definitions are an important cause of waste in health care. Now is the time to revise the definition of NAFLD to include only those who have developed advanced fibrosis.

Comment | | Nature Reviews Gastroenterology & Hepatology

In 2018, there have been substantial advances in our understanding of the risk factors for advanced liver disease in nonalcoholic fatty liver disease, including genetic variants and the gut microbiota. Promising results have also arisen from drugs targeting metabolic pathways involved in the progression of liver damage.

Year in Review | | Nature Reviews Gastroenterology & Hepatology

NAFLD, the hepatic manifestation of the metabolic syndrome, is a multifactorial condition — environmental factors influence an inherited genetic risk. Stender et al. now describe the additive effect of obesity and NAFLD-associated genetic polymorphisms on steatosis, elevated serum alanine aminotransferase levels and cirrhosis, remarkably illustrating the principle of gene–environment interactions.

News & Views | | Nature Reviews Gastroenterology & Hepatology

A recent study reports that being overweight in late adolescence is associated with an increased risk of liver-related morbidity and mortality later in life. These findings give further strength to the concerns for the deleterious effects of childhood obesity on liver health. Early prevention by screening and lifestyle modification should be advised by health policies.

News & Views | | Nature Reviews Gastroenterology & Hepatology